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Subjects

Abstract

Models of firing rate homeostasis such as synaptic scaling and the sliding synaptic plasticity modification threshold predict that decreasing neuronal activity (for example, by sensory deprivation) will enhance synaptic function. Manipulations of cortical activity during two forms of visual deprivation, dark exposure (DE) and binocular lid suture, revealed that, contrary to expectations, spontaneous firing in conjunction with loss of visual input is necessary to lower the threshold for Hebbian plasticity and increase miniature excitatory postsynaptic current (mEPSC) amplitude. Blocking activation of GluN2B receptors, which are upregulated by DE, also prevented the increase in mEPSC amplitude, suggesting that DE potentiates mEPSCs primarily through a Hebbian mechanism, not through synaptic scaling. Nevertheless, NMDA-receptor-independent changes in mEPSC amplitude consistent with synaptic scaling could be induced by extreme reductions of activity. Therefore, two distinct mechanisms operate within different ranges of neuronal activity to homeostatically regulate synaptic strength.

Acknowledgements

Research reported in this article was supported by the National Eye Institute of the National Institutes of Health under award number R01EY012124 (to A.K.), R01EY016431 (to E.Q.), R01EY025922 (to E.Q., A.K. and H.-K. L.) and R01-EY014882 (to H.-K.L.). A.K. was also supported by NIH grant P01 AG009973. M.C.D.B. was supported by grants T32EY007143 and T32HL110952.